Yang, Xiaolu and Chang, Howard Y. and Baltimore, David (1998) Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis. Science, 281 (5381). pp. 1355-1357. ISSN 0036-8075. doi:10.1126/science.281.5381.1355. https://resolver.caltech.edu/CaltechAUTHORS:20141124-102100187
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Abstract
Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2–like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.
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| Additional Information: | © 1998 American Association for the Advancement of Science. Received 3 June 1998; accepted 13 July 1998. We thank F. Chen and H. R. Horvitz for reagents and discussions, P. Svec and A. Darbinian for technical support, and V. M. Dixit, M. Gilman, S. L. Schreiber, and X. Wang for reagents. Supported by the Leukemia Society of America (to X.Y.), the Medical Scientist Training Program (to H.Y.C.), and NIH grant CA51462. | |||||||||
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| Issue or Number: | 5381 | |||||||||
| DOI: | 10.1126/science.281.5381.1355 | |||||||||
| Record Number: | CaltechAUTHORS:20141124-102100187 | |||||||||
| Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20141124-102100187 | |||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
| ID Code: | 52093 | |||||||||
| Collection: | CaltechAUTHORS | |||||||||
| Deposited By: | Tony Diaz | |||||||||
| Deposited On: | 24 Nov 2014 21:27 | |||||||||
| Last Modified: | 10 Nov 2021 19:20 |
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